Tetra-alkylated diamines



Patented Oct. 6, 1936 UNITED STATES TETRA-ALKYLATED DIAMINES Frank Lee Pyman and Hyman Henry Lionel Levene, Nottingham, England, assignors to Boots Pure Drug Company Limited, Nottingham, England, a British company No Drawing. Application June 6, 1935, Serial No. 25,342. In Great Britain June 26, 1934 11 Claims.

This invention relates to the production of tetra-alkylated-diamines, and more particularly to the production of tetra-alkyldiaminoderivatives of the parafiin series in which the number of carbon atoms of the hydrocarbon chain is any number from 8 to 12 inclusive, and the alkyl groups of the dialkylamino radicles are each either butyl or amyl groups. The tetra-alkylated-diamines which come into question are therefore of the general formula (CH2)n(NR1R2)2, where n is any number from 8 to 12 inclusive and R1 and R2 is each a butyl or amyl group. Some of these diamines have very considerable amoebicidal properties of the same order of activity as emetine, and are valuable, for example, in the treatment of dysentery and as emetine is relatively expensive and toxic, it is a desideratum to provide other substances having amoebicidal properties of the same order.

According to the present invention, the desired tetra-alkyldiamino derivative is formed by heating at a suitable temperature a dihalide, conveniently the dibromide of the corresponding hydrocarbon-(CI-h) Bra-with the appropriate secondary amine, NHRlRZ. It could not have been foreseen that the reaction could be made to proceed in this way to produce a considerable yield without the occurrence of secondary reactions to a substantial extent, nor could it have been foreseen that the derivatives when obtained would have any great therapeutic value as amoebicides.

The secondary amines required for use in the above reactions may be produced by hydrolysis of the corresponding para-toluenesulphonamides CH3-CsH4-SO2NR1R2-Whi0h may be Obtained by treating the sodium salt of para-toluenesulphonamide successively with alkyl bromides or other suitable derivatives such as alkyl chlorides or toluenesulphonates.

It will be understood that in carrying out the invention, the alkyl groups of the secondary bases may be varied, but in order that the invention may be clearly understood and readily carried into eifect, some particular examples of methods of carrying out the invention will now be more fully described.

Example 1 going forward in the following way:-

(CHz)1u H 4NH(C|Hn)2 :111: (CHI)IO(N l 2NH(C6HII)I,HB1' sHu Example 2 In the preparation of sym aK-di-n-amyldi-nbutyl-diamino-n-decane, 8 parts of aK-dibromdecane and 16 parts of n-amyl-n-butylamine are heated together under a condenser until a vigorous reaction commences. This is completed by heating the mixture on the steam bath for 24 20 hours. The mixture of oil and crystals is allowed tocool, mixed with dry ether and filtered, amylbutylamine hydrobromide remaining undissolved. The required base is isolated from the ether solution by distillation. It boils at 257262 C. at a pressure of 1'! mm. of mercury.

The n-amyl-n-butylamine used in the above example has a boiling point of 178 C. and may be produced by hydrolysis of para-toluenesulphonbutylamylamide, in the following manner. The sodium salt of para-toluenesulphonamide is heated in solution with butyl-toluenesulphonate to form para-toluenesulphonbutylamide, the sodium salt of which is then treated with amylbromide to form para-toluenesulphonbutylamylamide, which may be hydrolyzed with per cent sulphuric acid in the usual manner.

Example 3 In the preparation of aK-tetra-n-b'utyldiamino-n-decane, 15 parts of aK-dibromdecane and 26 parts of di-n-butylamine are heated together for 72 hours on the steam bath and the reaction mixture worked up as described in Example 3. The required base distills at 267 C. at a pressure of 30 mm. of mercury. The neutral tartrate of this base is a crystalline solid having a melting point of 87 C.

Example 4 In the preparation of wc-tetra-n-amyldiaminon-decane, 1 part of wc-dichlordecane and 3 parts of di-n-amylamine are heated together for 12 hours under reflux and the product worked up by either method described in the other examples.

The boiling points of some other members of the series of tetra-alkylated-diamines produced in accordance with the present invention have been determined and are as follows:

2%;? Boiling point w:-tetra-iso-amyldiamino-n-decane 6 235 C. aX-CGtI'a-IIQHIYIdiQmiDO n undecane; 18 272275 O. an-tetra-n-butyldiamino n dodecane l1 245 C.

We claim:- 1. The process for the production of a tetra- V alkyldiamino derivative of the paraffin series,

v of a hydrocarbon of the paraffin series containing a number of carbon atoms from 8 to 12 inclusive with a dialkylamine in which each of the two alkyl radicles is one of the group consisting of butyl and amyl until completion of the reaction, separating the desired derivative from the reaction mixture, and purifying said derivative by distillation.

3. The process for the production of a tetraalkyldiamino derivative of the paraflin series, which consists in the steps of heating a dibromide of a hydrocarbon of the parafiin series containing a number, of carbon atoms from 8 to 12 inclusive with a dialkylamine in which each of the two alkyl radicles is one of the group consisting of butyl and amyl until completion of the reaction, decomposing the alkylamine hydrobromide formed, and purifying the desired derivative by distillation.

4. The process for the production of a tetraalkyldiamino derivative of the paraffin series, which consists in the steps of heating a dibromide of a hydrocarbon of the parafiin series containing a number of carbon atoms from 8 to 12 inclusive with a dialkylaminel in which each of the two alkyl radicles is one of the group consisting of butyl and amyl until completion of the reaction, removing dialkylamine hydrobromide by filtration, and purifying the desired derivative by distillation.

5. The process for the production of arc-tetran-amyldiamino-n-decane, which comprises heating aK-dibromdecane with about four molecular proportions of di-n-amylamine until completion of the reaction, separating the desired derivative from the reaction mixture, and purifying said derivative by distillation.

6. The process for the production of sym oucdi-n-amyldi-n-butyldiamino-n decane, which comprises heating uK-dibromdecane with about four molecular proportions of n-butyl-n-amylamine until completion of the reaction, separating the desired derivative from the reaction mixture, and purifying said derivative by distillation.

7. The process for the production of mic-tetran-butyl-diaminon decane, which comprises heating uK-dibromdecane with about four molecular proportions of di-n-butylamine until completion of the reaction, separating the desired derivative from the reaction mixture, and purifying said derivative by distillation.

8. A tetra-alkyldiamino derivative of the par,- aflin series containing a number of carbon atoms from 8 to 12 inclusive in the hydrocarbon chain and in which each of the alkyl radicles of the dialkylamine group belongs to the group consisting of butyl and amyLsaid derivative having a high amoebicidal efficiency.

9. The amoebicidal product ax-tetra-n-amyldiamino-n decane. v

10. The amoebicidal product symaK-di-n-amyldi-n-butyldiamino-ndecane.

11. The amoebicidal product aK-tetra-n butyldiamino--n-decane..

FRANK LEE PYMAN. I-IYMAN HENRY LIONEL LEVENE. 

